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Potassium in Red Blood Cells - A New Biomarker of Oxidative Stress by Sepsis

Received: 12 September 2022    Accepted: 26 September 2022    Published: 11 October 2022
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Abstract

There is increasing evidence that oxidants and antioxidants play a key role in the pathogenesis of sepsis. Sepsis is also characterized by excessive production of oxidants. Although many biomarkers for oxidative stress have been developed, the most biomarkers are technically very complex and they are not suitable for clinical routine. We discuss the possibility of using as a biomarker for oxidative stress by sepsis a new parameter - the concentration of potassium in red blood cells (RBC). The method for measuring potassium in erythrocytes, as well as the explanation for the increased potassium in the RBC, as a result of eryptosis (absorption of released potassium), was described by us earlier. Oxidative stress is known to be a major trigger for eryptosis - as a consequence, the increased potassium concentration in RBC directly reflects the intensity of oxidative stress. We also detect a tight buffer-like interaction between potassium in RBC and chlorine in plasma. Based on results from our study, we designed a nomogram for acid-base status of RBC. Method: In 66 patients (meeting criteria "Sepsis-3"), measurements of potassium in RBC were performed on the 1st, 3rd and 5th day stay at intensive care unit (ICU). The results: all patients had increased potassium in RBC on the 1st day. In the RBC nomogram, all measurements were in the range of metabolic acidosis. Over time, potassium in RBC normalized in surviving patients (n=42). In deceased patients (n=24), potassium in RBC fell with transition to metabolic alkalosis. A clear relationship was also noted between the concentration of potassium in the RBC and SOFA scale. The transition from metabolic acidosis to the metabolic alkalosis was accompanied by increased mortality. So, ROC - analysis showed high sensitivity and specificity of RBC acid-base status in predicting in-hospital mortality (AUROC = 0,78). Conclusion: The preliminary diagnostic model created on the basis of the nomogram allows assess the relationship of this parameter with the clinical course of sepsis. Basically, three approaches are conceivable for clinical practice: 1. Estimation of oxidative stress; 2. Estimation of RBC insufficiency or potassium deficiency; 3. Monitoring of antioxidant therapy. For the introduction into clinical routine, the automation of the method by Medical Industry is essential.

Published in Clinical Medicine Research (Volume 11, Issue 5)
DOI 10.11648/j.cmr.20221105.14
Page(s) 135-144
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Potassium in Red Blood Cells, Ion-Selective Electrodes, Biological Marker, Oxidative Stress, Sepsis, Multiorgan-Failure

References
[1] E. Abraham, R. Wunderink, H. Silverman et al., “Efficacy andsafety of monoclonal antibody to human tumor necrosis factor alpha in patients with sepsis syndrome. A randomized, controlled, double-blind, multicenter clinical trial. TNFalpha MAb sepsis study group,” The Journal of the American Medical Association, vol. 273, no. 12, pp. 934–941, 1995.
[2] C. L. Sprung, D. Annane, D. Keh et al., “Hydrocortisone therapy for patients with septic shock,” The New England Journal of Medicine, vol. 358, no. 2, pp. 111–124, 2008.
[3] J. Fisher Jr., J. F. Dhainaut, S. M. Opal et al., “Recombinant human interleukin 1 receptor antagonist in the treatment of patients with sepsis syndrome. Results from a randomized, double-blind, placebo-controlled trial. Phase III rhIL-1ra Sepsis Syndrome Study Group,” The Journal of the American Medical Association, vol. 271, no. 23, pp. 1836–1843, 1994.
[4] R. C. Bone, C. J. Fisher Jr., T. P. Clemmer, G. J. Slotman, C. A. Metz, and R. A. Balk, “A controlled clinical trial of high-dose methylprednisolone in the treatment of severe sepsis andseptic shock,” The New England Journal of Medicine, vol. 317, no. 11, pp. 653–658, 1987.
[5] H. Sies, D. Jones, Oxidative stress, 2nd ed., in: G. Fink (Ed.), Encyclopedia of Stress, 3, Elsevier, Amsterdam (2007) 45–48.
[6] Mantzarlis K, Tsolaki V, Zakynthinos E. Role of Oxidative Stress and Mitochondrial Dysfunction in Sepsis and Potential Therapies. Oxid Med Cell Longev. 2017; 2017: 5985209. doi: 10.1155/2017/5985209. Epub 2017 Aug 20. PMID: 28904739; PMCID: PMC5585571.
[7] Cowley HC, Bacon PJ, Goode HF, Webster NR, Jones JG, Menon DK. Plasma antioxidant potential in severe sepsis: a comparison of survivors and nonsurvivors. Crit Care Med. 1996 Jul; 24 (7): 1179-83. doi: 10.1097/00003246-199607000-00019. PMID: 8674332.
[8] Chuang CC, Shiesh SC, Chi CH, Tu YF, Hor LI, Shieh CC, Chen MF. Serum total antioxidant capacity reflects severity of illness in patients with severe sepsis. Crit Care. 2006 Feb; 10 (1): R36. doi: 10.1186/cc4826. PMID: 16507162; PMCID: PMC1550865.
[9] Frijhoff J, Winyard PG, Zarkovic N, Davies SS, Stocker R, Cheng D, Knight AR, Taylor EL, Oettrich J, Ruskovska T, Gasparovic AC, Cuadrado A, Weber D, Poulsen HE, Grune T, Schmidt HH, Ghezzi P. Clinical Relevance of Biomarkers of Oxidative Stress. Antioxid Redox Signal. 2015 Nov 10; 23 (14): 1144-70. doi: 10.1089/ars.2015.6317. Epub 2015 Oct 26. PMID: 26415143; PMCID: PMC4657513.
[10] Nemkov T., Reisz J. A., Xia Y., Zimring J. C., D’Alessandro A. Red blood cells as an organ? How deep omics characterization of the most abundant cell in the human body highlights other systemic metabolic functions beyond oxygen transport. Expert Rev Proteomics 2018; 15 (11): 855 864, https://doi.org/10.1080/14789450.2018.1531710
[11] Pandey KB, Rizvi SI. Biomarkers of oxidative stress in red blood cells. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2011 Jun; 155 (2): 131-6. doi: 10.5507/bp.2011.027. PMID: 21804621.
[12] Lang E, Lang F. Triggers, inhibitors, mechanisms, and significance of eryptosis: the suicidal erythrocyte death. Biomed Res Int. 2015; 2015: 513518. doi: 10.1155/2015/513518. Epub 2015 Mar 4. PMID: 25821808; PMCID: PMC4364016.
[13] Pretorius E, du Plooy JN, Bester J. A Comprehensive Review on Eryptosis. Cell Physiol Biochem. 2016; 39 (5): 1977-2000. doi: 10.1159/000447895. Epub 2016 Oct 24. PMID: 27771701.
[14] Repsold L, Joubert AM. Eryptosis: An Erythrocyte's Suicidal Type of Cell Death. Biomed Res Int. 2018 Jan 3; 2018: 9405617. doi: 10.1155/2018/9405617. PMID: 29516014; PMCID: PMC5817309.
[15] Barg J. Verfahren und Vorrichtung für die Messung der Kaliumkonzentration in Erythrozyten [Apparatus for the measurement of potassium concentrations in erythrocytes, for medical laboratory diagnosis and scientific research, has a mixing chamber with distilled water and a reagent chamber as a disposable set]. Patent DE 000010308154 A1. 2004. URL: https://register.dpma.de/DPMAregister/pat/register?AKZ=103081542
[16] Astakhov А. А., Kazartsev V. V., Kuchkin K. V., Barg J. Ion-Selective Electrodes for Measuring Potassium in Erythrocytes: a Model for Clinical Interpretation of the Results (a Pilot Study). Sovremennye tehnologii v medicine 2022; 14 (3): 42, https://doi.org/10.17691/stm2022.14.3.05
[17] Sies H. Oxidative stress: a concept in redox biology and medicine. Redox Biol. 2015; 4: 180-3. doi: 10.1016/j.redox.2015.01.002. Epub 2015 Jan 3. PMID: 25588755; PMCID: PMC4309861.
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    Johannes Barg, Vitaliy Kazarcev, Alexey Astakhov. (2022). Potassium in Red Blood Cells - A New Biomarker of Oxidative Stress by Sepsis. Clinical Medicine Research, 11(5), 135-144. https://doi.org/10.11648/j.cmr.20221105.14

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    ACS Style

    Johannes Barg; Vitaliy Kazarcev; Alexey Astakhov. Potassium in Red Blood Cells - A New Biomarker of Oxidative Stress by Sepsis. Clin. Med. Res. 2022, 11(5), 135-144. doi: 10.11648/j.cmr.20221105.14

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    AMA Style

    Johannes Barg, Vitaliy Kazarcev, Alexey Astakhov. Potassium in Red Blood Cells - A New Biomarker of Oxidative Stress by Sepsis. Clin Med Res. 2022;11(5):135-144. doi: 10.11648/j.cmr.20221105.14

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  • @article{10.11648/j.cmr.20221105.14,
      author = {Johannes Barg and Vitaliy Kazarcev and Alexey Astakhov},
      title = {Potassium in Red Blood Cells - A New Biomarker of Oxidative Stress by Sepsis},
      journal = {Clinical Medicine Research},
      volume = {11},
      number = {5},
      pages = {135-144},
      doi = {10.11648/j.cmr.20221105.14},
      url = {https://doi.org/10.11648/j.cmr.20221105.14},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.cmr.20221105.14},
      abstract = {There is increasing evidence that oxidants and antioxidants play a key role in the pathogenesis of sepsis. Sepsis is also characterized by excessive production of oxidants. Although many biomarkers for oxidative stress have been developed, the most biomarkers are technically very complex and they are not suitable for clinical routine. We discuss the possibility of using as a biomarker for oxidative stress by sepsis a new parameter - the concentration of potassium in red blood cells (RBC). The method for measuring potassium in erythrocytes, as well as the explanation for the increased potassium in the RBC, as a result of eryptosis (absorption of released potassium), was described by us earlier. Oxidative stress is known to be a major trigger for eryptosis - as a consequence, the increased potassium concentration in RBC directly reflects the intensity of oxidative stress. We also detect a tight buffer-like interaction between potassium in RBC and chlorine in plasma. Based on results from our study, we designed a nomogram for acid-base status of RBC. Method: In 66 patients (meeting criteria "Sepsis-3"), measurements of potassium in RBC were performed on the 1st, 3rd and 5th day stay at intensive care unit (ICU). The results: all patients had increased potassium in RBC on the 1st day. In the RBC nomogram, all measurements were in the range of metabolic acidosis. Over time, potassium in RBC normalized in surviving patients (n=42). In deceased patients (n=24), potassium in RBC fell with transition to metabolic alkalosis. A clear relationship was also noted between the concentration of potassium in the RBC and SOFA scale. The transition from metabolic acidosis to the metabolic alkalosis was accompanied by increased mortality. So, ROC - analysis showed high sensitivity and specificity of RBC acid-base status in predicting in-hospital mortality (AUROC = 0,78). Conclusion: The preliminary diagnostic model created on the basis of the nomogram allows assess the relationship of this parameter with the clinical course of sepsis. Basically, three approaches are conceivable for clinical practice: 1. Estimation of oxidative stress; 2. Estimation of RBC insufficiency or potassium deficiency; 3. Monitoring of antioxidant therapy. For the introduction into clinical routine, the automation of the method by Medical Industry is essential.},
     year = {2022}
    }
    

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  • TY  - JOUR
    T1  - Potassium in Red Blood Cells - A New Biomarker of Oxidative Stress by Sepsis
    AU  - Johannes Barg
    AU  - Vitaliy Kazarcev
    AU  - Alexey Astakhov
    Y1  - 2022/10/11
    PY  - 2022
    N1  - https://doi.org/10.11648/j.cmr.20221105.14
    DO  - 10.11648/j.cmr.20221105.14
    T2  - Clinical Medicine Research
    JF  - Clinical Medicine Research
    JO  - Clinical Medicine Research
    SP  - 135
    EP  - 144
    PB  - Science Publishing Group
    SN  - 2326-9057
    UR  - https://doi.org/10.11648/j.cmr.20221105.14
    AB  - There is increasing evidence that oxidants and antioxidants play a key role in the pathogenesis of sepsis. Sepsis is also characterized by excessive production of oxidants. Although many biomarkers for oxidative stress have been developed, the most biomarkers are technically very complex and they are not suitable for clinical routine. We discuss the possibility of using as a biomarker for oxidative stress by sepsis a new parameter - the concentration of potassium in red blood cells (RBC). The method for measuring potassium in erythrocytes, as well as the explanation for the increased potassium in the RBC, as a result of eryptosis (absorption of released potassium), was described by us earlier. Oxidative stress is known to be a major trigger for eryptosis - as a consequence, the increased potassium concentration in RBC directly reflects the intensity of oxidative stress. We also detect a tight buffer-like interaction between potassium in RBC and chlorine in plasma. Based on results from our study, we designed a nomogram for acid-base status of RBC. Method: In 66 patients (meeting criteria "Sepsis-3"), measurements of potassium in RBC were performed on the 1st, 3rd and 5th day stay at intensive care unit (ICU). The results: all patients had increased potassium in RBC on the 1st day. In the RBC nomogram, all measurements were in the range of metabolic acidosis. Over time, potassium in RBC normalized in surviving patients (n=42). In deceased patients (n=24), potassium in RBC fell with transition to metabolic alkalosis. A clear relationship was also noted between the concentration of potassium in the RBC and SOFA scale. The transition from metabolic acidosis to the metabolic alkalosis was accompanied by increased mortality. So, ROC - analysis showed high sensitivity and specificity of RBC acid-base status in predicting in-hospital mortality (AUROC = 0,78). Conclusion: The preliminary diagnostic model created on the basis of the nomogram allows assess the relationship of this parameter with the clinical course of sepsis. Basically, three approaches are conceivable for clinical practice: 1. Estimation of oxidative stress; 2. Estimation of RBC insufficiency or potassium deficiency; 3. Monitoring of antioxidant therapy. For the introduction into clinical routine, the automation of the method by Medical Industry is essential.
    VL  - 11
    IS  - 5
    ER  - 

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Author Information
  • Retired from Anesthesiology Department, Asklepios City Hospital, Bad Wildungen, Germany

  • Department of Anesthesiology, South Ural State Medical University, Chelyabinsk, Russia

  • Department of Anesthesiology, South Ural State Medical University, Chelyabinsk, Russia

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